Question

Suppose a gene can suffer one of two types of deletion mutation. One mutation deletes 2 nucleotides in a row. The other mutation deletes 3 nucleotides in a row.

Which mutation will have the most impact following translation and why?

To support your answer, write out an example mRNA sequence and show the effects of each mutation on the corresponding amino acid sequence.

Answer 1

The mutation that deletes 2 nucleotides will be most impactful on following translation. This is because in mRNA the reading frame is such that each codon is made up of three nucleotides and codes for one amino acid. When the deletion of 3 nucleotides occurs, the overall reading framework won't be disturbed. Only an amino acid will be deleted from the overall protein. But, when 2 nucleotides are deleted, this will result in the formation of a protein with an entirely different sequence because the reading frame would be altered from and beyond the point of deletion.

Example:

mRNA:   5' AUGGUUCAGCUUAGCUAG 3'

Coded protein: N- Met-Val-Gln-Leu-Ser -C

Suppose the two nucleotides underlined above are deleted.

mRNA after deletion: 5' AUGGUUCAGCUUAGCUAG 3'

New protein after deletion: N- Met-Val-Ala -C

mRNA:   5' AUGGUUCAGCUUAGCUAG 3'

Now suppose the above three nucleotides underlined are deleted

mRNA after deletion: 5' AUGGUUCUUAGCUAG 3'

New protein after deletion: N- Met-Val-Leu-Ser -C.

We see that in case of a two deletions, a truncated peptide is produced because a stop codon rises according to the new reading frame.

But in case of three deletions, only a single amino acid Gln gets deleted but the other amino acids remain the same. Thus 2 deletions will be most impactful because it will give rise to a completely non-functional protein.

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